Biotechnology products, including recombinant viral vectors, typically involve introducing some genetic modification into eukaryotic cells and then growing these cells in a bioreactor or in multiple large cell culture dishes or vessels. Other important products include virus vaccine strains and modified live viruses.
For the production of a recombinant viral vectors, virus vaccine strains, and modified live viruses, a uniform cell source is needed to inoculate bioreactors or cell culture vessels. Typical cell sources include specific lines of genetically modified eukaryotic cells and controlled cell clones having cGMP status. This provides a basis for a Manufacturer's Working Cell Bank (MWCB). An MWCB consists of many aliquots (portions) of a cell suspension, each containing the same type of cells and approximately the same number of cells. These aliquots are prepared on the same day and frozen at the same time. The aliquots are then kept at very cold temperatures (cryopreserved). For each run, one or more of these aliquots of cells is thawed to provide the same starting point as any other run with the same cells.
Successful inoculation of a bioreactor or cell culture vessels with eukaryotic cells requires a minimum cell density to achieve proper cell growth. If the cell density is below the minimum level, additional time is required to achieve commercial cell growth levels, which adds expense to the process and increases the opportunity for contaminants to enter the cell environment. If the cell density is too high, the nutrients in the media can be depleted, which may result in reduced cell growth, lower cell productivity and possibly death of the cell culture.